Strong Anionic/Charge-Neutral Block Copolymers from Cu(0)-Mediated Reversible Deactivation Radical Polymerization

Despite recent developments in controlled polymerization techniques, the straightforward synthesis of block copolymers that feature both strong anionic and charge-neutral segments remains a difficult endeavor. In particular, solubility issues may arise during the direct synthesis of strong amphiphiles and typical postpolymerization deprotection often requires harsh conditions. To overcome these challenges, we employed Cu(0)-mediated reversible deactivation radical polymerization (Cu(0)-RDRP) on a hydrophobic isobutoxy-protected 3-sulfopropyl acrylate. Cu(0)-RDRP enables the rapid synthesis of the polymer, reaching high conversions and low dispersities while using a single solvent system and low amounts of copper species. These macromolecules are straightforward to characterize and can subsequently be deprotected in a mild yet highly efficient fashion to expose their strongly charged nature. Furthermore, a protected sulfonate segment could be grown from a variety of charge-neutral macroinitiators to produce, after the use of the same deprotection chemistry, a library of amphiphilic, double-hydrophilic as well as thermoresponsive block copolymers (BCPs). The ability of these various BCPs to self-assemble in aqueous media was further studied by dynamic light scattering, ζ-potential measurements as well as atomic force and electron microscopy.

Cyanopropan-2-yl propyl trithiocarbonate (CPP-TTC) was produced as reported elsewhere. 1 AIBN was recrystallized twice from methanol. Commercially-available monomers were passed through a short AlOx column to remove inhibitors prior to polymerizations. All other chemicals were used as received.
Stirring bars used for SET-LRP were winded with copper wire (4 cm) and etched in HCl solution for 30 minutes followed by extensively washed with deionized water, ethanol and acetone prior to polymerizations.
Me6-TREN/CuBr2 stock solutions were prepared freshly prior polymerization by introducing 1 eq CuBr2, 9 eq Me6-TREN and DMSO into a glass vial and thorough mixing. A calculated volume of the stock solution was introduced into the reaction mixture so to obtain 0.01 eq CuBr2 and 0.09 eq Me6-TREN respective to the initiator or macroinitiator. An example of stock solution is as following: CuBr2 (1 eq, 2.45 mg, 11.0 μmol), Me6-TREN (9 eq, 22.5 mg, 97.8 μmol) and DMSO (10.14 mL).
Spectra were analyzed with MestreNova software version 14.1.
Size-exclusion chromatography (SEC) was performed on a GPCMax system from Viscotek equipped with 302 TDA detectors array and two columns in series (PolarGel L and M, both 8 μm 30 cm) from Agilent Technologies. The columns and detectors were maintained at a temperature of 50 °C. DMF (≥ 99.9 %, Sigma-Aldrich) containing 0.01 M LiBr was used as eluent at a flow rate of 1 mL min -1 . Near monodisperse poly(methyl methacrylate) standards from Polymer Standard Services were used for the construction of a calibration curve. Samples were dissolved in the eluent at a concentration of ≈ 3 g L -1 and passed through a 0.45 μm PTFE filter prior to injection. Data acquisition and calculations were performed using Viscotek Omnisec software version 5.0. Differential scanning calorimetry (DSC) measurements were recorded on a TA instruments DSCQ1000. The samples (~ 5 mg) were subjected to the following method: (i) equilibration at -80 °C, (ii) 5 min isotherm, (iii) ramp to 100 °C at 10 °C min -1 , (iv) 5 min isotherm, (v) ramp to -80 °C at 10 °C min -1 , (vi) 5 min isotherm and (vii) ramp to 100 °C at 10 °C min -1 . Data analysis was performed on the second heating cycle using TA Instruments TRIOS software.
Thermogravimetric analysis (TGA) measurements were recorded on a TA instruments TGA5500 analyzer. The samples (~ 5 mg) were subjected to a 20 min isotherm at 130 °C to remove traces of solvent and moisture before returning to room temperature and zeroing the balance. Then, the samples were heated from 30 °C to 700 °C at a rate of 10 °C min -1 under a continuous nitrogen flow. The data acquisition and analysis was done using TA Instruments TRIOS software.
Dynamic light scattering (DLS) measurements were performed on a Malvern Panalytical Zetasizer Ultra system, equipped with a helium-neon laser (λ = 633 nm) and an Avalanche Photodiode detector. Samples were prepared at a concentration of 1 g L -1 in triple-filtered (0.2 5 μm cellulose acetate) 10 mM KNO3 solution. The nanoparticle solutions were measured at 25 °C in back scattering mode after 120 s equilibration time and using 30 cumulative recordings.
The LCST of the homopolymer was determined by measurements at a controlled temperature between 5 and 25 °C in back scattering mode, after 120 s equilibration time, using 30 cumulative recordings and at a fixed attenuator value (determined from a preliminary scan at 25 °C). Samples were recorded in triplicates. Results were analyzed with ZS Xplorer software. ζ-potential measurements were performed on a Malvern Panalytical Zetasizer ULtra system, equipped with a helium-neon laser (λ = 633 nm) and an Avalanche Photodiode detector. The measurements were taken at 25 °C while the acquisition times were determined automatically.
Samples were recorded in triplicates.
UV-Vis spectroscopy measurements were performed on a Jasco V-650 spectrophotometer equipped with a PAC-743 Peltier cell. Polymer solutions were prepared at a concentration of 1 g L -1 in triple-filtered (0.2 μm cellulose acetate) 10 mM KNO3 solution and cooled or heated by the Peltier cell per 1.0 ± 0.1 °C increments while being stirred at 200 rpm. Short transmittance spectra were recorded between 600 and 605 nm with 0.5 nm intervals and the value in that range was averaged. Samples were recorded in triplicates.
Transmission electron microscopy (TEM) imaging was performed on a Philips CM120 transmission electron microscope equipped with a tungsten filament and operated at an accelerating voltage of 120 kV. Images were acquired using a Gatan slow-scan CCD camera.
Negatively stained specimen were prepared by deposition of 5 μL of the nanoparticle dispersion (c ~ 1 g L -1 ) onto a glow-discharged (15 s at 50 mA and 300 V) 400-mesh copper grid with carbon support film and adsorption for 1 min before blotting. Before the specimen was fully dried, 5 μL of 2 wt.% uranyl acetate staining solution was deposited onto the grid, immediately blotted and a new 5 μL drop of staining solution was deposited and left to adsorb for 1 min before blotting. TEM images were analyzed using Image J software, using the software brightness and contrast correction tools to enhance the general quality of the snapshots and the software-imbedded measurement tool was utilized to determine the dimensions of the nanoparticles. The particles' diameter was measured center-to-center, i.e.
from the center of one particle to the center of the neighboring one.
Atomic force microscopy (AFM) imaging was performed in standard tapping mode in air using a Bruker Dimension 3100 system, equipped with VTESPA-300 tapping mode cantilevers from Bruker. Freshly-prepared C3M samples (1 g L -1 in 10 mM KNO3) were spin-coated (4 000 rpm, 60 s) onto a freshly-cleaved mica disc (Ø = 9.5 mm, muscovite mica grade V-1, Proscitech) and measured on the same day. Images were processed with Bruker NanoScope software.
The formation of complex coacervate core micelles (C3M) was done just before analysis.
Each polymer was dissolved in triple-filtered (0.

Synthesis of 3-isobutoxysulfopropyl acrylate (BSPA)
The synthesis of the monomer was adapted from a previously reported procedure. 1 KSPA (1 eq, 12.3 g, 52.9 mmol) and a stirring egg were charged in a 3-neck round bottom flask and subjected to several high vacuum / argon cycles to remove moisture before anhydrous DMF (40 mL) was added. The suspension was cooled over an ice bath before dropwise addition of All other Cu(0)-RDRP of BSPA were produced in a similar fashion, using the same amounts of BSPA and DMSO but lowering the amounts of EBiB, Me6-TREN and CuBr2 accordingly.
Detailed compositions of the reactions are summarized in Table S1. 9 The deprotection of poly(3-isobutoxysulfopropyl acrylate) was performed as reported before 1 and a typical procedure is as following (here depicted for the synthesis of PSPA-Na45): PBSPA45 (1 eq, 108 mg, 432 μmol BSPA) and NaI (

Synthesis of poly(ethylene oxide) macroinitiator (PEO90-Br)
Poly(ethylene oxide) was modified via esterification of the hydroxy group by treating the polymer with an excess acid halide, a method adapted from an earlier reported procedure. PMA92-b-PBSPA231 was prepared following the above-described procedure but using PMA92 (1 eq, 101.6 mg, 12.